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The arteriovenous fistula (AVF) has long been considered the optimal vascular access. However, the evolving characteristics of the ageing dialysis population limit the creation of an AVF in all patients. Thus, more patients start hemodialysis (HD) with a central venous catheter (CVC) rather than an AVF, and the supremacy of the AVF has recently been questioned. The aim of this study was to analyze the incidence and rate of access complications in 100 patients between 2010 and 2015. A total of 63 patients started HD with an AVF, while 37 began HD with a CVC. We found no differences in patient survival according to the vascular access in use at the beginning of dialysis, but patients were more likely to die while undergoing dialysis by means of a CVC than an AVF. Patients started on dialysis with a CVC had more cardiovascular disease, while patients who began dialysis with an AVF presented more hypertension. Fistulas presented a longer survival time despite more hospital admissions, but CVCs bore a higher risk of infections. Our results suggest that starting dialysis with a CVC does not confer a greater risk of death.

BACKGROUND AND AIMS Despite World Health Organisation recommends a salt intake of METHOD We conducted a single centre, cross-sectional, observational study enrolling patients older than 18, with a diagnosis of chronic kidney disease stage 3 to 5, who underwent a regular visit at the outpatient clinic of our Unit, from 12 March 2021 to 10 October 2021. Clinical data, including medical history, treatments and sociodemographic information were collected from patients’ records. Anthropometric measurements were performed during the visit. Every patient was asked to provide a random urine sample, to perform a 24-h urine collection and filled a questionnaire on Knowledge, Attitude and Practice toward salt that we adapted from other studies[1,2]; a section was focused on Mediterranean Diet adherence. Salt intake was assessed by means of 24-h sodium excretion and using three equations (namely Tanaka, Nerbass and Kawasaki) to estimate it from spot urine. Adequacy of 24-h urine collection was defined upon values of creatininuria. We evaluated whether there was a correlation between sodium intake with demographic and clinical data and with the scores from various sections of the questionnaire. RESULTS We enrolled 90 patients, 55 males and 35 females, aged 73.7 ± 8.7 years; mean BMI was 29.1 ± 5.5. Of 90 patients, 78 provided the 24-h urine collection; however, 30 out of 78 were not included due to inadequacy. Twenty-four hours sodium excretion of remaining 48 was compared with the estimates obtained from spot urine. Bland Altman test revealed best performance for Tanaka equation (bias 0.99 ± 62.5 mEq/d, 95% LoA from -121.6 to 123.6); thus, this was used for subsequent analysis. Mean sodium intake in our population was 156.2 ± 50.5 mEq/d. We found no difference in sodium intake according to gender, age, stage of CKD, blood pressure, education, smoking habits or residency; however, we found higher intake in overweight (148.5 ± 38.9 mEq/d) and obese (179.5 ± 62.4 mEq/d) people when compared with normal weight subjects (142.2 ± 43.1 mEq/d; P = 0.0301). Patients on diuretic treatment were found to have higher sodium intake (173.6 ± 58.6 versus 137.9 ± 30.7 mEq/d, P = 0.0018), but there was no association of sodium intake with number of antihypertensive medications. Although 63.3% of patients thought of consuming a diet with the right amount of salt, less than 10% of them knew exactly the recommended daily salt intake. We found no correlation between the questionnaire scores and clinical and sociodemographic data, even if female patients showed a trend toward better performance in Knowledge (P = 0.0756) and Mediterranean Diet adherence (P = 0.0632). A positive correlation between Knowledge and Practice scores was found (r = 0.3506, P = 0.0007). CONCLUSION Our study shows that the mean salt intake in chronic kidney disease patient is much higher than recommended, despite the importance of a low salt diet. Obese patients showed the highest sodium intake, possibly due to the elevate intake of processed food. The questionnaire showed a lack of knowledge that encompasses every sociodemographic category. Also, the high number of inadequate 24-h urine collections points out the critical role of the assessment method, which may need to be reconsidered.

Background and Aims Generalized edema, non responsive to oral diuretics, is one of the main causes of hospital admission for nephrotic syndrome patients. Although hospital length of stay (LOS) may vary widely, in 2017 the average LOS in acute-care hospitals was lower than 8 days in OECD countries. The aim of the present study was to determine the factors commonly associated with a longer LOS in patients admitted for edema due to nephrotic syndrome in the Nephrology Unit of ICS Maugeri, Pavia, Italy Method In this retrospective study we reviewed the medical records of all patients admitted for nephrotic syndrome between 2012-2020 in the Nephrology Unit of ICS Maugeri. Inclusion criteria were the following: age between 18-85 years of age; severe edema non responsive to oral, low dose diuretics; patients with heart failure, serum creatinine > 3.5 g/dl or on dialysis treatment were excluded from the study. Patients were divided into two groups according to the length of stay: ≤ 7 days or ≥ 8 days. Age, gender, serum protein concentration, creatinine, and hemoglobin; serum cholesterol and tryglicerides, urinary protein excretion rate; types of glomerular disease, weight loss were recorded. Student T tests and one-way Anova were performed to evaluate the differences between the means. Results 60 patients (42 male, 18 female) with a total number of hospital accesses of 93 were enrolled in the study. Mean age was 66.8 ± 13.07 years. Average LOS was 9.02 ± 7.4 days. Protein excretion rate was 6.7 ± 3.6 g/24 hours at the admission and was not statistically changed at discharge. Mean total serum protein and creatinine concentration at the admission were 4.7 ± 0.8 g/dl and 1.8 ± 1.1 mg/dl respectively. Patients with LOS < 7 days were younger (64 ± 11.9 vs 69 ± 13.6 years, p 0.001) and a significantly higher total serum protein concentration (5.02 ± 0.77 vs 4.65 ± 0.76 g/dl, p< 0.001) and haemoglobin (12.6 ± 1.8 vs 11.4 ± 1.8 g/dl, p< 0.05) compared to patients with longer LOS. Proteinuria was not significantly different between the two groups (6.27 ± 3.36 vs 7.1 ± 3.9 g/24 hours, p= NS). While serum cholesterol and tryglicerides were higher in the group of patients with longer LOS, weight loss was similar in the two groups at discharge. Although the difference was not significant, the group with longer hospitalization had a greater number of patients with a diagnosis of focal segmental glomerulosclerosis (FSGS) Conclusion Our results demonstrate that age, total serum protein concentration, serum creatinine, higher lipids and probably the diagnosis of FSGS may affect the hospital length of stay of patients with nephrotic syndrome admitted for severe edema. A more aggressive diuretic treatment may be needed in elderly nephrotic syndrome patients with lower GFR and total serum protein concentration.

Introduction Patients on dialysis (HDPs) are a category at high risk from COVID-19 and thus a high-priority group for vaccination. COVID-19 vaccine hesitancy has been a concern since the availability of the first vaccine. The objective of this study was to determine hesitancy rates and factors associated with hesitancy toward COVID-19 vaccination in HDP. Methods HDP were surveyed with an ad hoc questionnaire in 4 large dialysis facilities in Europe: Le Mans and Paris, in France, and Cagliari and Pavia, in Italy. The questionnaire explored different domains associated with vaccine hesitancy, such as perception of disease severity, sources of information about the vaccine and the disease, and confidence in the health care system. Results A total of 417 patients (average age 69 years, 60% men) agreed to answer the questionnaire. Hesitancy was associated with younger age (P = 0.003), lower perception of disease severity (P < 0.001) and vaccine efficacy (P < 0.001), and lower trust in vaccination (P < 0.001) and in the health care system and scientists (P < 0.001) in the univariate analysis. In the multivariate models, concerns about side effects (P = 0.004) and vaccine efficacy (P < 0.001) and living in France (P = 0.04) remained associated with higher vaccine hesitancy, whereas having received an influenza vaccine (P = 0.032) and trusting scientists (P = 0.032) were associated with a more positive attitude toward vaccination. Conclusions HDPs have a good understanding of the risks associated with COVID-19. Vaccine hesitancy was not associated with educational level, age, or gender but rather with lack of confidence in vaccine efficacy and concerns about safety. HDPs were quite skeptical about the health care system but generally trusted scientists.

Background and Aims The WHO has defined type II Diabetes Mellitus (DMII) as an epidemic disease. Indeed worldwide, diabetic patients are estimated to be 400 millions and this number is bound to grow in the next decades 1.Diabetic nephropathy (DN) develops in 20-40% of patients with DM 2.It is a condition generally characterized by presence of proteinuria and leads to a progressive reduction in kidney function and ultimately to End Stage Renal Disease (ESRD). Although DN represents a frequent complication in patients with DM it is well known that diabetic patients may develop kidney disease due to any other cause. Several studies have shown that about 30% of diabetic patients undergoing a kidney biopsy will be diagnosed with a non diabetic renal disease ( NDRD) 3.This suggests the importance of kidney biopsy in patients with DM.. Aim of our study was to evaluate the frequency of NDRD in our population, to identify pre-existing clinical or humoral parameters in patients with histological diagnosis of DN vs NDRD also evaluating the different clinical outcomes in patients with diagnosis of DN vs NDRD and identifying histological patterns of DN which may be associated to worst clinical outcomes. Method In this single centre retrospective observational study we evaluated all type II diabetic patients having undergone kidney biopsy in ICS Maugeri Spa SB in Pavia from May 2002 to December 2018 Results Our population included 71 patients with diagnosis of DMII having undergone kidney biopsy. Among these 36 (51%) had a histological diagnosis of DN, 29 ( 40%) of NDRD and 6 ( 9%) had both DN+NDRD. Of the NDRD patients 21% were diagnosed with membranous nephropathy 17% with nephroangiosclerosis, 10% with focal segmental glomerulosclerosis and 10% acute tubular necrosis.We found DN patients compared to NDRD had a greater DM II vintage (12 years vs 9,5 years), higher HbA1C (7,4% vs 6,5%, p2) and worsening of proteinuria and creatinine over a 24 month period although not statistically significant probably due to small sample size Conclusion In a population of DMII patients undergoing kidney biopsy 40% of patients had NDRD. NDRD appeared to have better clinical outcome ( lower proteinuria and lower creatinine) over time probably as a result of targeted therapy, also degree of gloerular damage in DN correlated with worse prognosis. Although some pre-exhisting conditions such as diabetic retinopathy are highly predictable of DN diagnosis our data supports the essential role of kidney biopsy in diabetic patients.Alltogether our data demonstrates the value of performing kidney biopsy in DMII patients

Background and Aims Potassium (K) is mostly an intracellular ion, with a complex homeostasis that is deeply modified in ESRD patients undergoing hemodialysis (HD). Several factors (diet, insulin, acid-base balance, aldosterone, etc) may contribute to determine the level of serum extracellular K, but it is not clear which factor contributes the most. We aimed to evaluate the importance of several factors in inducing hyperkalemia in HD patients. Methods Chronic tri-weekly HD patients were evaluated. Patients on diuretics or on potassium binders were excluded. For every patient we recorded age, sex, Kt/V and we measured the post-HD kalemia on the day before the long interHD interval. On the day after the long interHD interval we evaluated: pre-HD K, glucose, creatinine, aldosterone, LDH, CPK, arterial blood gases, ECG, overhydration by bioelectrical impedance analysis, body weight increase after the long interHD interval and daily urinary output. K amount introduced by diet was calculated by a dietitian from each patient’s daily food diary. Treatment with ARB, ACE-inhibitors, beta-blockers, insulin or heparin was recorded. Data are presented as mean±SD for each variable analyzed. Correlations between the serum K values and change in serum K (delta K) and the other patient medical data were determined through the two-tailed Pearson’s test or Spearman test according to data distribution. Results We enrolled 56 patients (male 53.6%), aged 72±13, with a mean Kt/V 1.44±0.25. Mean post-HD kalemia was 3.65±0.4 mmol/L, mean pre-HD kalemia was 5.23±0.72 mmol/L, with a mean delta 1.58±0.64 mmol/L. Medium pH was 7.37±0.01, with serum bicarbonate 20.15±4.0 mmol/L. Overhydration estimated by bioelectrical impedance analysis was 2.3±0.6 L, while mean daily intake of K was 1697.13±711.13 mg. We found a strong positive correlation between delta K and pre-HD kalemia (r=0.79, p Conclusion Potassium homeostasis is markedly altered in ESRD and several factors contribute to determine the serum K values. In this study we found that delta potassium correlates to pre-HD kalemia. We did not study the temporal kinetic of K increase, but it is reasonable to infer that a significant post-HD rebound may contribute to increase kalemia, as dietary intake of K was not found to correlate to delta K or to serum K after the long interdialytic interval. The positive correlation between delta K and serum bicarbonate is unexpected and difficult to explain. However, since we did not measure serum bicarbonate post-HD, we may speculate that patients with high delta K and serum bicarbonate might have even higher levels of bicarbonate after HD. In conclusion, our study shows that none of the examined factors prevales in determining high serum potassium in HD patients.

Background: Smart Flow is an innovative tool available on the Carestream Touch Prime Ultrasound machines, which provides automated blood flow measurement and shows the vectors that form the blood flow in the vessel. We compared the use of Smart Flow with traditional Duplex Doppler Ultrasound to evaluate blood flow of arteriovenous fistulas in prevalent hemodialysis patients. Methods: A total of 31 chronic patients on hemodialysis were enrolled. Blood flow was measured on the brachial artery with Smart Flow and duplex Doppler ultrasound. In a subset of 26 patients, a video of the juxta-anastomotic efferent vein was recorded and analyzed to calculate an index of flow turbulence. Results: We enrolled 21 males and 10 females aged 68.52 ± 11.64 years at the time of evaluation with an average arteriovenous fistulas vintage of 50.23 ± 47.42 months and followed them up for 18.03 ± 5.18 months. Smart Flow and Duplex Doppler Ultrasound blood flow measurements positively correlated (p Conclusion: Smart Flow is reliable, reproducible, and faster than traditional duplex ultrasound. However, the additional information given by the Smart Flow technique does not seem to add any further benefits in terms of prediction of the access failure.

Kidney transplantation (KT) immunosuppression may induce bone tissue damage with bone mineral density (BMD) loss increasing bone fractures risk. Steroid therapy is considered the major player, but others factors are still under review.We designed an observational retrospective cohort study to evaluate bone damage after KT. The prevalence of osteopenia, osteoporosis, bone fractures, and the associated risk factors were investigated. The following parameters were recorded before transplantation and at the last follow-up: demographic indexes, cumulative steroid dose (CSD), dialytic and transplantologic age, previous nephropathy, femoral and lumbar BMD, fractures, immunosuppressors, calcemia, phosphoremia, rejection episodes, estimated glomerular filtration rate, and parathyroid hormone and vitamin D levels. Stata software (Stata Corporation, College Station, Texas, United States) was used for the statistical analysis, to perform the Fisher's exact test, Kruskal-Wallis test, Student t test, as well as univariate and multivariate analyses.The analyzed cohort was composed of 297 patients (65.3% males and 34.7% females). Sixty percent of KT patients had normal BMD, 24% had osteopenia, and 15% had osteoporosis. Twelve percent were victims of bone fractures (8.4% minor, 2% femoral, and 1.7% vertebral). A significant correlation (P .05) was observed for both osteopenia and osteoporosis with menopause, transplantologic age, CSD, previous glomerulonephritis, and mammalian target of rapamycin (mTOR) inhibitors treatment (imTOR).This study confirms the correlation between CSD (both before and after transplantation) and post-transplantation bone damage. It also shows that a large fraction of these patients had normal BMD related with a low steroid dose in our protocols. This correlation between imTOR assumption and osteoporosis deserves attention and warrants further in vitro analyses to be performed.

Costimulatory pathways play a key role in immunity, providing the second signal required for a full activation of adaptive immune response. Different costimulatory families (CD28, TNF-related, adhesion and TIM molecules), characterized by structural and functional analogies, have been described. Costimulatory molecules modulate T cell activation, B cell function, Ig production, cytokine release and many other processes, including atherosclerosis. Patients suffering from renal diseases present significant alterations of the costimulatory pathways, which might make them particularly liable to infections. These alterations are further pronounced in patients undergoing kidney transplantation. In these patients, different costimulatory patterns have been related to distinct clinical features. The importance that costimulation has gained during the last years has led to development of several pharmacological approaches to modulate this critical step in the immune activation. Different drugs, mainly monoclonal antibodies targeting various costimulatory molecules (i.e. anti-CD80, CTLA-4 fusion proteins, anti-CD154, anti-CD40, etc.) were designed and tested in both experimental and clinical studies. The results of these studies highlighted some criticisms, but also some promising findings and now costimulatory blockade is considered a suitable strategy, with belatacept (a CTLA-4 fusion protein) being approved as the first costimulatory blocker for use in renal transplantation. In this review, we summarize the current knowledge on costimulatory pathways in the setting of kidney transplantation. We describe the principal costimulatory molecule families, their role and clinical significance in patients undergoing renal transplantation and the new therapeutic approaches that have been developed to modulate the costimulatory pathways.

L'iperbilirubinemia severa si associa spesso al danno renale acuto (AKI), soprattutto in pazienti con livelli di bilirubinemia pari a 20–25 mg/dL. Considerando la potenziale tossicità renale della bilirubina, è possibile che la rimozione di tale sostanza dal plasma rappresenti un modo per migliorare la funzione renale nei pazienti con AKI associato a iperbilirubinemia. Qui presentiamo il caso di un uomo di 47 anni, ricoverato per ittero ingravescente e ascite. All'anamnesi il paziente presentava una mielofibrosi idiopatica, associata a epatopatia con valori di bilirubina stabili intorno ai 4 mg/dL. Al momento del ricovero, la bilirubinemia era pari a 45 mg/dL, con valori di creatininemia di 2.1 mg (valore precedente 0.7 mg/dL). La biopsia epatica mostrava un quadro di severa colangite linfogranulocitaria. Per il peggioramento del quadro ematochimico (bilirubinemia 59.7 mg/dL e creatininemia 4 mg/dL), una volta escluse cause funzionali di insufficienza renale e la sindrome epato-renale, sospettando un danno renale da iperbilirubinemia, abbiamo iniziato il trattamento con plasma adsorbimento/perfusione (PAP). Tale metodica si basa sulla rimozione selettiva della bilirubina dal plasma mediante una specifica resina adsorbente. Dopo il trattamento, si assisteva a una riduzione dei livelli di bilirubina sierica fino a 24 mg/dL, associata a un significativo miglioramento della funzione renale. Tuttavia, circa dieci giorni dopo l'inizio della PAP, il paziente decedeva per shock settico. Questo caso rappresenta un'ulteriore prova della potenziale nefrotossicità della bilirubina, suggerendo che la PAP potrebbe essere una valida opzione terapeutica nei pazienti con danno renale acuto secondario a iperbilirubinemia.

Vascular accesses are essential for effective dialysis treatment. Arteriovenous fistulas, grafts and central venous catheters are the options available to the nephrologist, but they all have their pros and cons. All of the 3 types of vascular access share the same complications but at different rates, and their costs vary enormously, with on balance the arteriovenous fistula being the best choice. Nevertheless, recently the number of incident patients starting dialysis treatment with a venous catheter as vascular access has been steadily increasing. This is true even for more advanced countries such as the United States, where despite the efforts made to promote the use of fistulas, their prevalence is still low compared with Europe. Moreover, nowadays nephrologists are required to master technical skills that once were those of surgeons and to perform interventions to preserve the patency of the access. The aim of this paper is to review the prevalence, benefits and complications of the different vascular accesses in light of the most recent findings.

To the Editor: van Slambrouck et al.1 proposed the term bile cast nephropathy to describe the high prevalence of tubular bile casts in the kidneys of patients with jaundice and renal injury of different origin, suggesting a potential direct nephrotoxicity of bilirubin. This observation not only highlights an important pathogenetic mechanism, but also leads to hypothesize that bilirubin removal per se could improve renal function in jaundiced patients. Recently, we had the possibility to explore this intriguing hypothesis.

Background: Ischemia-reperfusion (I/R) is present at various degrees in kidney transplants. I/R plays a major role in early function and long-term survival of renal allograft. The purpose of our study was to determine if immunosuppressants modulate I/R in a model that separates I/R from all immune responses. Methods: Sprague-Dawley rats with monolateral renal I/R received daily cyclosporine (A), tacrolimus (B), sirolimus (C) or saline (D). Sham-operated rats received saline (E). After 30 days, glomerular filtration rate for each kidney was measured by inulin clearance. Kidney injury was examined, and TGF-β, fibronectin and metalloproteases were evaluated by real-time PCR, Western blot and zymography. Results: Sirolimus, but not cyclosporine and tacrolimus, prevented a glomerular filtration rate decrease in I/R kidneys (403 ± 303 vs. 1,006 ± 484 µl/min, p < 0.05; 126 ± 170 vs. 567 ± 374 µl/min, p < 0.05; 633 ± 293 vs. 786 ± 255; A, B and C group, respectively, I/R vs. contralateral kidneys). Sirolimus reduced ED-1+ cell infiltrate, interstitial fibrosis and intimal thickening of small vessels observed in I/R kidneys of controls and calcineurin inhibitor-treated rats. Tacrolimus and cyclosporine increased fibronectin and TGF-β expression and matrix deposition. Only sirolimus increased metalloprotease activity. Conclusions: Sirolimus but not calcineurin inhibitors prevented I/R-induced kidney injury.

Mesangial cell (MC) proliferation and production of extracellular matrix or loss of MC are both central findings in a number of renal proteinuric diseases. However, the role of MC as components of the glomerular filtration barrier and whether MC alterations induce changes in the glomerular filtration barrier leading to proteinuria are still matters of debate. The effects of Sirolimus (SRL) in proteinuric nephropathies is controversial: some papers have indicated a reduction and others, an increase in proteinuria after sirolimus treatment. Considering the pivotal role of MC in the pathogenesis of many chronic nephropathies, we evaluated the effect of SRL on cultured human MC. We treated primary human MC cultures with SRL, or platelet-derived growth factor (PDGF) or SRL + PDGF, or dimethylsulfoxide, the SRL vehicle, as a control. PDGF was used to activate MC. After 48 hours treatment, MC showed a significant growth increase that was significantly reduced by SRL (P < .01). Apoptosis, determined by the TUNEL assay and flow cytometry, was not modified by the treatments at 24 hours. SRL treatment increased significantly the number of alpha-smooth muscle actin-positive cells compared with controls (P < .05). Cells treated with SRL and SRL + PDGF showed significant changes in morphology with increased mean cell surface, perimeter, and maximum diameter (P < .01) but not protein content. Furthermore, MC treated with SRL showed decreased migration through polycarbonate membranes. The changes induced by SRL may help to explain some of the in vivo effects observed in SRL-treated patients.

Erythropoietin-stimulating agents (ESAs) are commonly used to treat anemia in kidney transplant recipients (KTRs). Since 2007, continuous erythropoietin receptor activator (CERA) has been one of the newest recombinant ESAs to treat anemia in dialysis and nondialysis patients with chronic kidney disease. The efficacy of CERA to manage anemia has not been extensively evaluated in KTRs. We evaluated safety, efficacy, and satisfaction among KTRs treated with CERA. We enrolled 19 anemic KTRs (60 ± 9.3 y) who were treated with short-acting ESA for ≥24 weeks. They were shifted to the equivalent dose of CERA and followed for 24 weeks. We measured serum hemoglobin, hematocrit, creatinine, iron, ferritin, and transferrin. To investigate tolerance to and satisfaction with short-acting ESA and CERA, questionnaires were administered to the patients before shifting to CERA and at the end of the follow-up. After 6 months, CERA induced an increase in hemoglobin levels (12.3 ± 0.8 vs 11.2 ± 1.1 g/dL; P = .002, CERA vs short-acting ESA, respectively). In 2 patients treatment was discontinued because the hemoglobin increased to >13 g/dL. No significant differences were observed in serum iron and creatinine between short-acting ESA and CERA throughout the study. The questionnaires showed better compliance to CERA treatment with reduced pain at the injection site, which led subjects to prefer CERA to short-acting ESA. In summary, CERA showed better control of anemia compared with short-acting ESA. It was preferred by the majority of patients, mainly because of the reduced number of monthly injections. Our results demonstrated CERA to be effective, safe, and well tolerated in the management of anemia in KTRs.